Hypotensive episodes at 24-h Ambulatory Blood Pressure Monitoring predict adverse outcomes in Parkinson’s Disease

Hypotensive episodes at 24-h Ambulatory Blood Pressure Monitoring predict adverse outcomes in Parkinson’s Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Hypotensive episodes at 24-h Ambulatory Blood Pressure Monitoring predict adverse outcomes in Parkinson’s Disease Fabrizio Vallelonga, Matteo Valente, Marta Maria Tangari, Anna Covolo, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3904996/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Apr, 2024 Read the published version in Clinical Autonomic Research → Version 1 posted 4 You are reading this latest preprint version Abstract Purpose. Neurogenic orthostatic hypotension (nOH) is a frequent non-motor feature of Parkinson’s disease (PD), associated with adverse outcomes. Recently, 24-hour ambulatory BP monitoring (ABPM) has been shown to diagnose nOH with good accuracy (in the presence of at least 2 episodes of systolic BP drop ≥ 15 mmHg compared to the average 24-h). This study aims at evaluating the prognostic role of ABPM-hypotensive episodes in predicting PD disability milestones and mortality and comparing it to well-defined prognostic role of nOH. Methods. PD patients who underwent ABPM from January 2012 to December 2014 were retrospectively enrolled and assessed for the development of falls, fractures, dementia, bed/wheelchair confinement, hospitalization, mortality, during an up-to-10-year follow-up. Results. Ninety-nine patients (male 74%; age: 64.0 ± 10.1 years; PD duration: 6.4 ± 4.0 years) were enrolled. At baseline, 38.4% of patients had ABPM-hypotensive episodes and 46.5% had bedside nOH. At Kaplan-Meier analysis patients with ABPM-hypotensive episodes had an earlier onset of falls (p = 0.001), fractures (p = 0.004), hospitalizations (p = 0.009), bed/wheelchair confinement (p = 0.032), dementia (p = 0.001), and showed a shorter survival (8.0vs9.5 years; p = 0.009). At Cox regression analysis (adjusted for age, disease duration, Charlson Comorbidity Index, and H&Y stage at baseline) a significant association was confirmed between ABPM-hypotensive episodes and falls (OR:3.626; p = 0.001), hospitalizations (OR:2.016; p = 0.038), and dementia (OR:2.926; p = 0.008), while bedside nOH was only associated with falls (OR 2.022; p = 0.039) and dementia (OR:1.908; p = 0.048). Conclusion. The presence of at least two ABPM-hypotensive episodes independently predicted the development of falls, dementia, and hospitalization, showing a stronger prognostic value than the simple bedside assessment. Parkinson’s disease orthostatic hypotension disability milestones adverse outcomes ambulatory blood pressure monitoring hypotensive episodes Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Orthostatic hypotension (OH) may affect at least 30% of patients with Parkinson’s disease (PD) [ 1 ][ 2 ][ 3 ], potentially resulting in dramatic complications, such as falls, fractures, head trauma, wheelchair/bed confinement and hospitalization, with a significantly increased mortality risk [ 4 ][ 5 ]. Moreover, recent evidence underlines the possible association between OH and cognitive impairment and cerebral atrophy [ 6 ][ 7 ][ 8 ][ 9 ]. Current diagnostic criteria for OH rely on office blood pressure (BP) measurements demonstrating a sustained drop of at least 20 mmHg (systolic) or 10 mmHg (diastolic) after 3 min of standing from a supine position [ 10 ]. Although useful in clinical practice, this definition remains anchored to an artificial assessment that only partially recapitulates the complexity of circadian BP fluctuations occurring during daily living activities [ 11 ]. In fact, these criteria are affected by a limited reproducibility (79% in neurogenic OH (nOH) and 67% in non-neurogenic OH) [ 12 ][ 13 ], with a maximal level of error for BP measurements carried out during the afternoon [ 14 ]. Therefore, the presence of OH may be largely underestimated. In this context, the 24-hour ambulatory blood pressure monitoring (ABPM), a validated technique for the assessment of arterial blood pressure [ 15 ], could represent a reliable instrument for the detection of OH and autonomic neuropathy (AN) [ 16 ][ 17 ]. A recent study from our group [ 18 ], based on the evaluation of several ABPM parameters, demonstrated that having more than 2 episodes of systolic drop ≥ 15 mmHg during the waking period, compared to the average 24-hours systolic BP, resulted in a reproducible measure for the diagnosis of nOH, yielding high accuracy and specificity values. In this study we sought to investigate, in a large cohort of parkinsonian patients, the potential prognostic role of ABPM-hypotensive episodes in predicting mortality and specific OH-associated complications (falls, fractures, bed/wheelchair confinement, cognitive impairment), thus informing on possible different trajectories of PD progression. Moreover, we aim to evaluate their role in informing on key healthcare economic indicators such as the presence of hospitalizations. Finally, we compare them to office nOH, an established predictor of adverse outcomes [ 4 ][ 19 ]. METHODS We retrospectively evaluated a cohort of PD patients. In order to reach a long-term observational time, we included patients who underwent ABPM at our center during the period comprised between January 2012 and December 2014 and followed-up with periodic neurological assessment for at least three years. Cohort selection Parkinsonian patients were screened for the following inclusion/exclusion criteria: Inclusion criteria Diagnosis of PD per the UK Brain Bank criteria [ 20 ]; stable dosage of dopaminergic and vasoactive (antihypotensive and/or anti- hypertensive) medications for at least 4 weeks prior to ABPM; presence of ABPM and OH assessment, performed between January 2012 and December 2014. Exclusion criteria Chronic heart failure, chronic renal failure, diabetes mellitus, amyloidosis, autoimmune disorders, malignancies, or other diseases potentially associated with secondary forms of autonomic dysfunction [ 21 ]. Patients without constant periodic neurological follow-up (at least every 12–18 months), and/or complete medical records, and/or follow-up duration of at least 3 years (except for patients dead before the 3-year threshold) were also excluded. Baseline Evaluation Clinical and neurological evaluation All patients underwent a standardized clinical evaluation including medical history collection, vital parameters, complete physical examination, and PD staging by means of the Hoehn and Yahr (H&Y) scale [ 22 ]. Finally, Charlson comorbidity index was assessed [ 23 ]. Office blood pressure measurement Office BP evaluations were carried out between 2 PM and 5 PM, at least 2 h after a meal, in a standardized environment at a room temperature of 71–75° Fahrenheit. BP values were collected in the supine position (average of the last three BP stable measurements) and every minute during the active standing position with an OMRON automatic sphygmomanometer (HEM-9219T-E, Japan ©). Heart rate (HR) values were also collected. OH was defined as a sustained systolic BP drop ≥ 20 mm Hg or a diastolic BP drop ≥ 10 mm Hg within 3 min of orthostatic test [ 10 ]. We included in the OH analyses only patients with nOH, defined as having a Δ HR/Δ systolic BP ratio < 0.5 beats per minute (bpm)/mmHg [ 24 ]. Ambulatory Blood Pressure Monitoring Twenty-four hours ABPMs were performed with a portable device (Spacelabs 90207, Spacelabs Inc., Redmond, WA, USA ©) with appropriate cuff size placed on the non-dominant arm as per the current guidelines [ 15 ]. BP measurements were taken every 15 min during the daytime and nighttime. Patients were asked to keep a diary of occupational activities, sleep, and awake time, as well as the time of meals. We used normal reference thresholds for ABPM and adhered to the definition of weighted BP variability and dipping patterns proposed by the European Society of Hypertension [ 15 ]. According to a previous study from our group [ 18 ] we defined hypotensive episode (Hypo-ep ∆15/24h ) a systolic drop ≥ 15 mmHg compared to the average 24-h systolic BP, during the waking period (from awakening to lunch). We considered as significant the presence of at least two hypotensive episodes [ 18 ]. Follow-up evaluation We retrospectively reviewed the medical records of each participant. For every outpatient visit we evaluated: the medical history, which included information on treatment, recent falls, fractures, ER accesses and hospitalizations; the neurological evaluation, including the staging of PD motor severity assessed by means of the H&Y scale; and the cognitive status. Dementia was diagnosed when Montreal Cognitive Assessment (MoCA) score was lower than 21/30 [ 25 ], or when reported at recent comprehensive neuropsychological assessment, or in the presence of incontrovertible symptoms/signs of cognitive impairment associated with functional limitation (e.g., executive or amnestic impairment needing assistance in common activities of daily living) [ 26 ]. Mortality data were searched in our electronic archives, which are constantly updated by the regional registry office. Outcome Measures and Statistical analysis The potential prognostic role of ABPM hypotensive episodes (Hypo-ep ∆15/24h ) in predicting specific complications, was compared with a well-established predictor, such as office nOH. Primary endpoints included mortality for all causes, falls, fractures, and cognitive impairment. Secondary endpoints included hospitalizations, and bed or wheelchair confinement. Cumulative survival for each adverse outcome was evaluated through Kaplan-Meier curves. The sample was divided in patients with and without the following predictors: a) at least two hypotensive episodes (Hypo-ep ∆15/24h ) at the ABPM during the waking period; b) office nOH. Differences between the two groups were assessed by means of the log-rank test. The prognostic role of the same predictors was then evaluated through Cox regression analysis, adjusting for age, Charlson comorbidity index, PD duration and severity (H&Y scale). In both Kaplan-Meier and Cox regression analyses, patients already reporting the adverse outcome at baseline (e.g., patients reporting falls or dementia) were excluded. Continuous variables were expressed as mean ± standard deviation. Qualitative variables were expressed as frequencies or percentage values. Normal distribution of continuous variables was tested using the Shapiro-Wilk test. Differences between two independent groups were evaluated using a Student’s t-test for continuous variables with normal distribution and the Mann-Whitney test for continuous variables with non-normal distribution. Categorical variables were compared using the chi-square test or Fisher’s exact test according to sampling number of analysed groups. Statistical analysis was performed with SPSS (IBM Corp. Released 2017. IBM SPSS, Version 25.0. Armonk, NY: IBM Corp). Statistical significance was considered for p values < 0.05. The present study was approved by the Institutional Review Committee of Turin (Comitato Etico Interaziendale A.O.U. Città della Salute e della Scienza di Torino – A.O. Ordine Mauriziano). All subjects submitted their written informed consent. RESULTS Inclusion criteria were fulfilled by 143 patients; 44 patients presented exclusion criteria (n = 3 had chronic heart failure, n = 4 had chronic renal failure, n = 12 had diabetes mellitus, n = 12 had incomplete clinical data at baseline, n = 13 had incomplete clinical data at follow-up, or were lost at follow-up). Therefore, the study population consisted of 99 patients, with a higher prevalence of men (74%), a mean age of 64.0 ± 10.1 (range 34–79) years, and PD duration of 6.4 ± 4.0 (range 1–18) years. The average follow-up duration was 5.9 ± 2.7 years (range 1–10). At baseline, 45 patients (45.5%) presented with H&Y stage 1, 38 (38.4%) with stage 2, 15 (15.2%) with stage 3, and one (1.0%) with stage 4, while no patients met the clinical criteria of H&Y stage 5. Previous history of arterial hypertension was present in the 29.3% of patients (n = 29). All patients were on dopaminergic treatment, with a levodopa equivalent daily dose (LEDD) of 662.0 ± 352.7 mg, while the 31.3% (n = 31) of the cohort was on vasoactive drugs (antihypertensive (n = 31) and/or antihypotensive (n = 24) medications). OH was detected in 48 patients, but in two cases the Δ HR/ Δ BP ratio indicated the presence of non-neurogenic OH. The remaining 46 nOH patients (46.5%) were included in the analyses. ABPM detected at least two hypotensive episodes (≥ 2 Hypo-ep ∆15/24h ) in 38 patients (38.4%). Clinical and demographical characteristics of patients with and without hypotensive episodes at ABPM are shown in Table 1 . Sensibility (67.4%), specificity (86.8%), and accuracy (77.8%) of the Hypo-ep ∆15/24h criterion for the detection of nOH were comparable to those found in our previous study on a different PD population [ 18 ], confirming the consistency of the method. Table 1 Demographic and clinical characteristics. Overall (n. 99) w/ Hypo-ep (n. 38) w/o Hypo-ep (n.61) p-value Age [years] 64.0 ± 10.1 67.8 ± 10.1 61.7 ± 9.5 0.003 Female sex [n.] (%) 26 (26.3) 10 (26.3) 16 (26.2) 0.992 Disease duration [years] 6.4 ± 4.0 7.1 ± 4.4 5.9 ± 3.6 0.163 Follow-up duration [years] 5.9 ± 2.7 5.2 ± 2.5 6.3 ± 2.7 0.035 Total LEDD [mg] 662.0 ± 352.7 757.1 ± 381.7 602.8 ± 322.6 0.034 Vasoactive therapy [n.] (%) 31 (31.3) 17 (44.7) 14 (22.9) 0.023 Previous arterial hypertension [n.] (%) 29 (29.3) 16 (42.1) 13 (21.3) 0.027 nOH [n.] (%) 46 (46.5) 31 (81.6) 15 (24.5) < 0.001 Ambulatory blood pressure monitoring 24h SBP [mmHg] 119.7 ± 10.4 121.5 ± 9.9 118.6 ± 10.6 0.191 24h MBP [mmHg] 88.1 ± 7.8 89.5 ± 7.6 87.3 ± 7.8 0.170 24h DBP [mmHg] 71.8 ± 7.5 72.3 ± 7.6 71.4 ± 7.4 0.541 Daytime SBP [mmHg] 121.6 ± 10.9 121.5 ± 10.0 121.7 ± 11.5 0.949 Daytime MBP [mmHg] 89.9 ± 8.6 90.0 ± 8.1 90.0 ± 8.9 0.968 Daytime DBP [mmHg] 73.9 ± 8.0 73.4 ± 7.9 74.2 ± 8.1 0.664 Daytime HR [bpm] 76.8 ± 9.5 76.8 ± 11.0 76.8 ± 8.5 0.982 Nighttime SBP [mmHg] 115.2 ± 14.7 122.1 ± 16.5 110.9 ± 11.7 0.001 Nighttime MBP [mmHg] 83.8 ± 11.0 89.1 ± 12.4 80.5 ± 8.5 < 0.001 Nighttime DBP [mmHg] 66.9 ± 9.8 70.7 ± 11.5 64.6 ± 7.7 0.006 Nighttime HR [bpm] 65.3 ± 8.9 67.3 ± 9.3 64.1 ± 8.6 0.087 Daytime SBP load [%] 19.7 ± 20.9 21.4 ± 18.2 18.7 ± 22.6 0.528 Daytime DBP load [%] 17.0 ± 19.0 18.1 ± 17.6 16.4 ± 19.9 0.653 Nighttime SBP load [%] 33.7 ± 33.5 49.2 ± 36.7 24.0 ± 27.4 0.001 Nighttime DBP load [%] 34.0 ± 31.3 47.6 ± 35.1 25.5 ± 25.4 0.001 Reverse dipping [n.] (%) 30 (30.3) 19 (50.0) 11 (18.0) 0.001 w-BPV [mmHg] 12.1 ± 3.8 14.6 ± 4.5 10.6 ± 2.2 < 0.001 Hypo-ep Δ15/24 h [n.] 2.1 ± 3.3 5.2 ± 3.5 0.3 ± 0.4 < 0.001 Office blood pressure values SBP (supine) [mmHg] 130.6 ± 16.5 140.0 ± 17.1 124.8 ± 13.3 < 0.001 DBP (supine) [mmHg] 79.1 ± 8.9 82.9 ± 8.5 76.7 ± 8.3 < 0.001 HR (supine) [bpm] 75.8 ± 11.3 77.8 ± 12.8 74.5 ± 10.2 0.151 SBP (orthostatism 1’) [mmHg] 116.0 ± 21.0 118.2 ± 25.2 114.6 ± 17.9 0.405 DBP (orthostatism 1’) [mmHg] 74.9 ± 11.6 76.2 ± 12.8 74.1 ± 10.9 0.389 SBP (orthostatism 3’) [mmHg] 115.5 ± 18.4 116.8 ± 21.8 114.8 ± 16.0 0.600 DBP (orthostatism 3’) [mmHg] 74.7 ± 10.7 75.0 ± 12.1 74.5 ± 9.9 0.825 HR (orthostatism) [bpm] 84.8 ± 13.2 85.2 ± 15.3 84.5 ± 11.8 0.817 LEDD: levodopa equivalent daily dose; nOH: neurogenic orthostatic hypotension; SBP: systolic blood pressure; MBP; mean blood pressure; DBP: diastolic blood pressure; BPV: blood pressure variability; Hypo-ep Δ15/24 h : hypotensive episode at Ambulatory Blood pressure Monitoring; HR: heart rate; w-BPV: weighted blood pressure variability; w/: with; w/o: without Patients with hypotensive episodes were older and treated with higher doses of dopaminergic therapy; they had 3-fold higher prevalence of nOH (p < 0.001) and 2-fold higher prevalence of arterial hypertension (p = 0.027). Moreover, they showed higher nocturnal BP values (p = 0.001), BP loads (p = 0.001) and BP variability (p < 0.001), together with a 3-fold higher prevalence of reverse dipping pattern (p = 0.001) (Table 1 ). At baseline, the prevalence of falls in the entire sample was 14.1% (n = 14), significantly higher in patients with hypotensive episodes at ABPM (26.3% vs. 6.6%, p = 0.008). Dementia was reported in 10.1% of patients (n = 10), with a 2-fold higher prevalence (15.8% vs. 6.6%) among patients with hypotensive episodes at ABPM, not reaching the statistical threshold (p = 0.128). No patient was bedridden/wheelchair-bound or reported recent fractures or hospitalization. Outcome evaluation During the follow-up, we observed a high incidence of falls (40.0%; 34/85, excluding patients already reporting falls at baseline), dementia (37.1%; 33/89, excluding patients already demented at baseline), fractures (22.2%; 22/99), hospitalization (32.3%; 32/99), and bed or wheelchair confinement (13.1%; 13/99). Mortality rate was 13.1% (13/99), with a mean survival time from baseline of 5.7 ± 2.7 years and a mean disease duration at death of 15.3 ± 6.1 years. Both incidence and prevalence of falls were significantly higher in patients with ABPM hypotensive episodes (Incidence: 57.1% vs. 31.6%, p = 0.022; Prevalence: 68.4% vs. 36.1%, p = 0.002). The same observations were found for dementia (Incidence: 53.1% vs. 28.1%, p = 0.017; Prevalence: 60.5% vs. 32.8%, p = 0.006). Patients with ABPM hypotensive episodes presented with significant higher incidence of fractures (34.2% vs. 14.8%, p = 0.023), while for hospitalization and bed/wheelchair confinement the difference did not reach full statistical significance (42.1% vs. 26.2%, p = 0.078; and 21.1% vs. 8.2%, p = 0.064; respectively). Mortality was higher in patients with ABPM hypotensive episodes, with a trend towards statistical significance (21.1% vs. 8.2%, p = 0.064). The Kaplan-Meier analysis revealed that the presence of hypotensive episodes at ABPM was associated with earlier onset of falls (4.9 years (95% CI 3.8-6.0) vs. 7.9 years (7.1–8.7); p = 0.001), fractures (6.4 years (95% CI 5.3–7.6) vs. 9.0 years (8.4–9.6); p = 0.004), hospitalizations (5.3 years (95% CI 4.1–6.4) vs. 8.2 years (95% CI 7.4-9.0); p = 0.009), bedridden/wheelchair confinement (7.1 years (95% CI 6.6–7.7) vs. 9.4 years (95% CI 8.8–9.9); p = 0.032), and dementia (5.0 years (95% CI 4.0–6.0) vs. 8.1 years (7.2–8.9); p = 0.001). Patients with hypotensive episodes at ABPM also showed a shorter survival (8.0 years (95% CI 7.3–8.7) vs. 9.5 years (95% CI 9.0–10.0); p = 0.009) (Fig. 1). Office OH was related to earlier onset of falls (5.8 years (95% CI 4.7-7.0) vs. 7.7 years (6.9–8.6); p = 0.045), earlier development of cognitive impairment (6.0 years (95% CI 5.0–7.0) vs. 7.8 years (95% CI 6.9–8.7); p = 0.034), and death (8.0 years (95% CI 7.3–8.7) vs. 9.5 years (9.1–10.0); p = 0.048), while a trend towards statistical significance was observed for hospitalizations (p = 0.086), fractures (p = 0.089), and bedridden/wheelchair confinement (p = 0.057) (Fig. 2). After correction for potential confounders, such as age, Charlson comorbidity index, PD duration, and PD severity at baseline, the Cox-Regression analysis showed a significant association between the presence of hypotensive episodes at ABPM and falls (OR 3.626, 95% CI 1.7–7.6; p = 0.001), hospitalizations (OR 2.016, 95% CI 1.2–4.5; p = 0.038), and dementia (OR 2.926, 95% CI 1.3–6.5; p = 0.008); the association with fractures (OR 2.155, 95% CI 0.9–5.4; p = 0.092) showed a trend towards statistical significance, while no association was found with bed/wheelchair confinement (OR 2.462, 95% CI 0.7–8.5; p = 0.155) or mortality (OR 1.352, 95% CI 0.4–5.1; p = 0.655). After the same corrections, office nOH showed inferior prognostic value for the adverse outcomes considered, only presenting a significant association with falls (OR 2.022, 95% CI 1.2–4.1; p = 0.039) and dementia (OR 1.908, 95% CI 1.1-4.0; p = 0.048). Details are presented in Fig. 3. DISCUSSION OH is a frequent and detrimental feature of PD; however, in clinical practice its diagnosis is still overlooked. One of the main features limiting a correct OH detection in an outpatient setting is the presence of BP circadian fluctuations. In this context, we explored the prognostic role of hypotensive episodes detected at the ABPM in predicting mortality and specific adverse outcomes in a large cohort of parkinsonian patients. We retrospectively evaluated mortality and the occurrence of important milestones of disability during an up-to-10-year follow-up and compared them between patients with and without ABPM hypotensive episodes. Finally, we evaluated the same differences between patients with and without office nOH. We found a significant association between ABPM hypotensive episodes and earlier onset of falls, cognitive impairment, hospitalizations, fractures, being bedridden or wheelchair-bound, and mortality. After correcting for potential confounders, hypotensive episodes retained a significant correlation with higher risk of falls, hospitalizations, and cognitive impairment. On the other hand, office nOH was associated with earlier onset of falls, cognitive impairment, and death, but only falls and cognitive impairment maintained the association after the adjusted analysis. Association with falls . nOH is a well-known risk factor for falls in general population, and it is considered one of the main issues to be targeted to reduce the risk of falls, together with functional status, home safety, and vision disturbances [ 27 ]. In PD patients, OH is independently associated with an up-to-10-fold higher risk ok falls [ 5 ]. However, daily BP profile is characterized by significant circadian fluctuations, and is influenced by many intrinsic and extrinsic features, such as sleep, temperature, meals, fluid intake, exercise, evaluation setting (e.g., in-hospital vs. home), and drugs intake. Therefore, the simple in-office evaluation of OH could be burdened by a certain amount of inaccuracy, while the evaluation by means of ABPM could led to a more detailed identification of hypotensive episodes, besides providing important information on supine hypertension, a frequently overlooked feature of cardiovascular dysautonomia [ 28 ]. Our results seem to confirm this assumption, since both ABPM episodes and office OH were associated with higher risk of falls, but the former showed a stronger and more significant correlation. Association with cognitive impairment. The association of OH and cognitive impairment has been detected both in general population and in patients with Alzheimer’s Disease or vascular dementia [ 29 ][ 30 ][ 31 ]. Large population studies highlighted an increased risk of developing dementia in patients with OH, ranging from 1.2-to-2-fold [ 32 ]. This association results even stronger in α-synucleinopathies, with a 3-to-8-fold higher risk of cognitive impairment in PD patients with OH [ 6 ][ 32 ][ 33 ]. Possible pathophysiological mechanisms are multiple and still to be fully clarified [ 8 ]. While some authors postulate a phenotypical association between dysautonomia, cognitive impairment, and worse motor impairment [ 34 ], other works reported that repeated bouts of cerebral hypoperfusion, along with altered regional patterns in supine cerebral blood flow and the presence of supine hypertension, could lead to greater burden of white matter lesions and cerebral atrophy, thus favoring the development of cognitive impairment [ 35 ][ 9 ][ 32 ][ 36 ]. However, these two hypotheses are not mutually exclusive, and both diffuse pathology and cerebral hypoperfusion may play a synergistic role [ 9 ]: the possibility exists that, in the context of a diffuse neurodegeneration, chronic OH and impaired dynamic cerebral auto-regulation [ 37 ] contribute to the worsening of neuropathology, probably by means of hypoxia-induced neurodegeneration, rather than by favoring α-synuclein deposition or vascular pathology [ 38 ]. In our study, we observed a significant association between ABPM hypotensive episodes (and in-office OH) and dementia, even after adjusting our analyses for many confounding variables that may explain the phenotypical association between OH and dementia (i.e., age, Charlson comorbidity index, PD duration and motor severity), thus suggesting a prevalent causative or synergistic role of OH in determining cognitive impairment. This observation seems in line with the recent findings by Ruiz Barrio and colleagues [ 38 ], who in a large pathological study on PD and Multiple System Atrophy patients observed an independent association between OH and cognitive impairment, but did not find differences in α-synuclein, β-amyloid, or tau pathology in patients with and without OH. Finally, in the present study, the strength and the significance of the association with cognitive impairment was greater for ABPM hypotensive episodes than office OH, further confirming the usefulness of ABPM in capturing the complexity of the circadian fluctuation of BP, and suggesting a possible role of BP variability in determining worse functional outcomes [ 39 ]. Association with hospitalization. About 80,000 hospitalizations in the United States each year are related to OH, mainly in the elderly population [ 40 ][ 41 ]. In PD patients, OH is an independent determinant of greater health care utilization [ 1 ], both for the potential consequences of the hypotensive episodes (falls, syncopes, head injury, fractures) and for the presence of other clinical features potentially responsible for hospitalization, which usually coexist with OH, such as ageing, diabetes, and cardiovascular comorbidities [ 42 ]. In our sample, ABPM hypotensive episodes were significantly associated with a 3-year earlier need for hospitalization and a 2-fold higher risk of hospitalization, compared to patients without episodes. Surprisingly, office OH did not show significant correlation at the adjusted Cox regression analysis, possibly due to the long-term follow-up in a relatively aged population, which resulted in a high probability of observing hospitalization for causes other than OH. Association with fractures and bed/wheelchair confinement. Although univariate Kaplan-Meier analysis showed earlier occurrence of fractures and bed or wheelchair confinement in patients with hypotensive episodes or office OH, similarly to previous reports [ 43 ][ 44 ], these observations were not confirmed at the corrected analysis, probably due to the inclusion, among the considered confounders, of age, disease duration, and motor disability, which are well-known features associated with these detrimental disability milestones in PD and other α-synucleinopathies [ 45 ][ 46 ][ 47 ]. Association with mortality. Autonomic dysfunction [ 48 ] and, specifically, OH [ 49 ] have been associated with shorter survival in PD. In our sample, mortality was significantly associated with ABPM episodes and OH, with a 1.5-year shorter survival. However, the corrected analyses did not confirm this association, probably due to the relatively low rate of death during the follow-up. The main strengths of our study include the long-term follow-up, with seriate and standardized clinical evaluations, as well as rigorous patients’ selection. However, some limitations should be taken into account. First, the relatively low sample size. Second, the retrospective design may have hampered the collection of important clinical data, including the disability milestones considered in the study, although we included only patients with a periodic and standardized follow-up in order to minimize this possible bias. Third, the absence of seriate collection of office OH or ABPM data, may have underestimated the incidence of new OH; however, if this were the case, we would have probably observed an even greater association between hypotensive episodes and disability milestones or mortality. Fourth, the definition of nOH was not based on cardiovascular autonomic test assessment, although the application of the recently proposed Δ HR/Δ systolic BP index [ 24 ] should have attenuated this bias. Fifth, the lack of a comprehensive evaluation of the autonomic symptoms other than OH limits firm considerations on a causal relationship between hypotensive episodes/OH and the development of disability milestones. In conclusion, our findings highlight the potential role of repeated hypotensive episodes in determining worse outcomes in PD patients, confirming and strengthening, by means of a 10-year follow-up, previous Literature data. Though, our study introduces a novel element that has so far received little consideration. In fact, we demonstrated the usefulness of ABPM in predicting detrimental PD complications, with apparent greater accuracy compared to simple OH bedside evaluation, due to its higher capability in capturing the complexity of BP circadian fluctuations. Thus, a wider application of ABPM, both in clinical practice and in research context, is warranted to enhance the comprehension of the relationship between cardiovascular dysautonomia and PD progression trajectories. Declarations CONFLICT OF INTEREST Financial disclosure FVa, MV, MMT, AC, VM, CD, GS, MG, FVe, LL, SM: None AR: he received grant support and speaker honoraria from Abbvie, speaker honoraria from Chiesi Farmaceutici and travel grants from Lusofarmaco, ChiesiFarmaceutici, Medtronic, and UCB Pharma. AM: he received supported from the NIH (KL2 TR001426), speaker honoraria from CSL Behring, Abbvie, Abbott, Theravance and Cynapsus Therapeutics. He has received grant support from Lundbeck and Abbvie Competing interests and Funding : none References Merola A, Sawyer RP, Artusi CA et al (2018) Orthostatic hypotension in Parkinson disease: Impact on health care utilization. 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Neurology 75:1717–1725. https://doi.org/10.1212/WNL.0b013e3181fc29c9 (2013) Diagnostic and statistical manual of mental disorders: DSM-5™, 5th ed. American Psychiatric Publishing, Inc., Arlington, VA, US Ganz DA, Latham NK (2020) Prevention of Falls in Community-Dwelling Older Adults. N Engl J Med 382:734–743. https://doi.org/10.1056/NEJMcp1903252 Vallelonga F, Maule S (2019) Diagnostic and therapeutical management of supine hypertension in autonomic failure: a review of the literature. J Hypertens 37:1102–1111. https://doi.org/10.1097/HJH.0000000000002008 Cremer A, Soumaré A, Berr C et al (2017) Orthostatic Hypotension and Risk of Incident Dementia: Results From a 12-Year Follow-Up of the Three-City Study Cohort. Hypertens (Dallas, Tex 1979) 70:44–49. https://doi.org/10.1161/HYPERTENSIONAHA.117.09048 Min M, Shi T, Sun C et al (2018) The association between orthostatic hypotension and dementia: A meta-analysis of prospective cohort studies. Int J Geriatr Psychiatry 33:1541–1547. https://doi.org/10.1002/gps.4964 Allan LM, Ballard CG, Allen J et al (2007) Autonomic dysfunction in dementia. J Neurol Neurosurg Psychiatry 78:671–677. https://doi.org/10.1136/jnnp.2006.102343 Robertson AD, Udow SJ, Espay AJ et al (2019) Orthostatic hypotension and dementia incidence: links and implications. Neuropsychiatr Dis Treat 15:2181–2194. https://doi.org/10.2147/NDT.S182123 Pilotto A, Romagnolo A, Tuazon JA et al (2019) Orthostatic hypotension and REM sleep behaviour disorder: impact on clinical outcomes in α-synucleinopathies. J Neurol Neurosurg Psychiatry 90:1257–1263. https://doi.org/10.1136/jnnp-2019-320846 Fereshtehnejad S-M, Romenets SR, Anang JBM et al (2015) New Clinical Subtypes of Parkinson Disease and Their Longitudinal Progression: A Prospective Cohort Comparison With Other Phenotypes. JAMA Neurol 72:863–873. https://doi.org/10.1001/jamaneurol.2015.0703 Robertson AD, Messner MA, Shirzadi Z et al (2016) Orthostatic hypotension, cerebral hypoperfusion, and visuospatial deficits in Lewy body disorders. Parkinsonism Relat Disord 22:80–86. https://doi.org/10.1016/j.parkreldis.2015.11.019 Palma JA, Redel-Traub G, Porciuncula A et al (2020) The impact of supine hypertension on target organ damage and survival in patients with synucleinopathies and neurogenic orthostatic hypotension. Park Relat Disord 75:97–104. https://doi.org/10.1016/j.parkreldis.2020.04.011 Chen H, Xu E, Zhou F et al (2022) Impaired dynamic cerebral autoregulation: A potential mechanism of orthostatic hypotension and dementia in Parkinson’s disease. Front Aging Neurosci 14:927009. https://doi.org/10.3389/fnagi.2022.927009 Barrio IR, Miki Y, Jaunmuktane ZT et al (2022) Association Between Orthostatic Hypotension and Dementia in Patients With Parkinson Disease and Multiple System Atrophy. https://doi.org/10.1212/WNL.0000000000201659 . Neurology Asmuje NF, Mat S, Myint PK, Tan MP (2022) Blood Pressure Variability and Cognitive Function: a Scoping Review. Curr Hypertens Rep 24:375–383. https://doi.org/10.1007/s11906-022-01200-w Shibao C, Grijalva CG, Raj SR et al (2007) Orthostatic hypotension-related hospitalizations in the United States. Am J Med 120:975–980. https://doi.org/10.1016/j.amjmed.2007.05.009 Grijalva CG, Biaggioni I, Griffin MR, Shibao CA (2017) Fludrocortisone Is Associated With a Higher Risk of All-Cause Hospitalizations Compared With Midodrine in Patients With Orthostatic Hypotension. J Am Heart Assoc 6. https://doi.org/10.1161/JAHA.117.006848 Feldstein C, Weder AB (2012) Orthostatic hypotension: a common, serious and underrecognized problem in hospitalized patients. J Am Soc Hypertens 6:27–39. https://doi.org/10.1016/j.jash.2011.08.008 Finucane C, O’Connell MDL, Donoghue O et al (2017) Impaired Orthostatic Blood Pressure Recovery Is Associated with Unexplained and Injurious Falls. J Am Geriatr Soc 65:474–482. https://doi.org/10.1111/jgs.14563 Nakamura T, Suzuki M, Ueda M et al (2020) Impact of orthostatic hypotension on wheelchair use in patients with Parkinson’s disease. J Neural Transm 127:379–383. https://doi.org/10.1007/s00702-019-02127-4 Koo HY, Cho E, Bin, Kong SH et al (2023) Fracture risk in Parkinson’s disease according to its severity and duration. Osteoporos Int a J Establ as result Coop between. Eur Found Osteoporos Natl Osteoporos Found USA 34:81–89. https://doi.org/10.1007/s00198-022-06562-0 De Pablo-Fernández E, Lees AJ, Holton JL, Warner TT (2019) Prognosis and Neuropathologic Correlation of Clinical Subtypes of Parkinson Disease. JAMA Neurol 76:470–479. https://doi.org/10.1001/jamaneurol.2018.4377 Zhang L, Hou Y, Gu X et al (2023) Prediction of early-wheelchair dependence in multiple system atrophy based on machine learning algorithm: A prospective cohort study. Clin Park Relat Disord 8:100183. https://doi.org/10.1016/j.prdoa.2023.100183 De Pablo-Fernandez E, Tur C, Revesz T et al (2017) Association of autonomic dysfunction with disease progression and survival in Parkinson disease. JAMA Neurol 74:970–976. https://doi.org/10.1001/jamaneurol.2017.1125 Goldstein DS, Holmes C, Sharabi Y, Wu T (2015) Survival in synucleinopathies: A prospective cohort study. Neurology 85:1554–1561. https://doi.org/10.1212/WNL.0000000000002086 Cite Share Download PDF Status: Published Journal Publication published 24 Apr, 2024 Read the published version in Clinical Autonomic Research → Version 1 posted Reviewers agreed at journal 31 Jan, 2024 Reviewers invited by journal 31 Jan, 2024 Editor assigned by journal 30 Jan, 2024 First submitted to journal 27 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3904996","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":270541677,"identity":"4a8a692d-d839-4d54-9187-dadfeea20a07","order_by":0,"name":"Fabrizio 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07:25:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3904996/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3904996/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10286-024-01030-7","type":"published","date":"2024-04-25T00:54:04+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50746067,"identity":"7a51c89d-5f27-4ad2-a792-f506bb770eb5","added_by":"auto","created_at":"2024-02-06 17:05:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":306122,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eHypotensive episodes at Ambulatory Blood Pressure Monitoring were associated with earlier onset of falls (A), fractures (B), hospitalizations (C), bedridden/wheelchair confinement (D), dementia (E), and shorter survival (F) (see manuscript for details). w/o: without; w/: with; Hypo-ep: at least 2 hypotensive episodes at Ambulatory Blood Pressure Monitoring\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure1KMHypoEpDEFINITIVE.png","url":"https://assets-eu.researchsquare.com/files/rs-3904996/v1/485e764903def576e35ede90.png"},{"id":50746065,"identity":"92543491-c92c-43db-859e-6a41bf07b40a","added_by":"auto","created_at":"2024-02-06 17:05:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":315760,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003enOH detected at office evaluation was associated with earlier onset of falls (A), dementia (E), and shorter survival (F), while no association was present for fractures (B), hospitalizations (C), and bedridden/wheelchair confinement (D) (see manuscript for details). w/o: without; w/: with; nOH: neurogenic orthostatic hypotension\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure2KMnOHDEFINITIVE.png","url":"https://assets-eu.researchsquare.com/files/rs-3904996/v1/716ba742c54eaac32483b369.png"},{"id":50746066,"identity":"c34aaeda-0921-49d8-92fb-86c5c7a0f5d3","added_by":"auto","created_at":"2024-02-06 17:05:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":159471,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eHypotensive episodes at Ambulatory Blood Pressure Monitoring, even after correcting for potential confounders, were significantly associated with falls, hospitalization, and dementia; nOH detected at the office evaluation was associated only, and with lower power and significance, with falls and dementia (see manuscript for details). Hypo-ep: hypotensive episodes at Ambulatory Blood Pressure Monitoring; nOH: neurogenic orthostatic hypotension; Continuous line: Hypotensive episodes confidence intervals; dotted line: neurogenic orthostatic hypotension confidence intervals; green line: significant association between predictor and adverse outcome; red line: non-significant association between predictor and adverse outcome\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure3.CoxregressionDEFINITIVE.png","url":"https://assets-eu.researchsquare.com/files/rs-3904996/v1/ba9e27ab44c66bdd89ce3ff2.png"},{"id":55698248,"identity":"a35e22f2-8fe9-494d-8a93-3e5b64e54302","added_by":"auto","created_at":"2024-05-02 02:28:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":887668,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3904996/v1/4420e23a-5e17-40ce-bdfe-0f33d95f7233.pdf"}],"financialInterests":"","formattedTitle":"Hypotensive episodes at 24-h Ambulatory Blood Pressure Monitoring predict adverse outcomes in Parkinson’s Disease","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eOrthostatic hypotension (OH) may affect at least 30% of patients with Parkinson\u0026rsquo;s disease (PD) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e][\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e][\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], potentially resulting in dramatic complications, such as falls, fractures, head trauma, wheelchair/bed confinement and hospitalization, with a significantly increased mortality risk [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e][\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Moreover, recent evidence underlines the possible association between OH and cognitive impairment and cerebral atrophy [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e][\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e][\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e][\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Current diagnostic criteria for OH rely on office blood pressure (BP) measurements demonstrating a sustained drop of at least 20 mmHg (systolic) or 10 mmHg (diastolic) after 3 min of standing from a supine position [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Although useful in clinical practice, this definition remains anchored to an artificial assessment that only partially recapitulates the complexity of circadian BP fluctuations occurring during daily living activities [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In fact, these criteria are affected by a limited reproducibility (79% in neurogenic OH (nOH) and 67% in non-neurogenic OH) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e][\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], with a maximal level of error for BP measurements carried out during the afternoon [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Therefore, the presence of OH may be largely underestimated.\u003c/p\u003e \u003cp\u003eIn this context, the 24-hour ambulatory blood pressure monitoring (ABPM), a validated technique for the assessment of arterial blood pressure [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], could represent a reliable instrument for the detection of OH and autonomic neuropathy (AN) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e][\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A recent study from our group [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], based on the evaluation of several ABPM parameters, demonstrated that having more than 2 episodes of systolic drop\u0026thinsp;\u0026ge;\u0026thinsp;15 mmHg during the waking period, compared to the average 24-hours systolic BP, resulted in a reproducible measure for the diagnosis of nOH, yielding high accuracy and specificity values.\u003c/p\u003e \u003cp\u003eIn this study we sought to investigate, in a large cohort of parkinsonian patients, the potential prognostic role of ABPM-hypotensive episodes in predicting mortality and specific OH-associated complications (falls, fractures, bed/wheelchair confinement, cognitive impairment), thus informing on possible different trajectories of PD progression. Moreover, we aim to evaluate their role in informing on key healthcare economic indicators such as the presence of hospitalizations. Finally, we compare them to office nOH, an established predictor of adverse outcomes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e][\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eWe retrospectively evaluated a cohort of PD patients. In order to reach a long-term observational time, we included patients who underwent ABPM at our center during the period comprised between January 2012 and December 2014 and followed-up with periodic neurological assessment for at least three years.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCohort selection\u003c/h2\u003e \u003cp\u003eParkinsonian patients were screened for the following inclusion/exclusion criteria:\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eInclusion criteria\u003c/strong\u003e \u003cp\u003eDiagnosis of PD per the UK Brain Bank criteria [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]; stable dosage of dopaminergic and vasoactive (antihypotensive and/or anti- hypertensive) medications for at least 4 weeks prior to ABPM; presence of ABPM and OH assessment, performed between January 2012 and December 2014.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eExclusion criteria\u003c/strong\u003e \u003cp\u003eChronic heart failure, chronic renal failure, diabetes mellitus, amyloidosis, autoimmune disorders, malignancies, or other diseases potentially associated with secondary forms of autonomic dysfunction [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Patients without constant periodic neurological follow-up (at least every 12\u0026ndash;18 months), and/or complete medical records, and/or follow-up duration of at least 3 years (except for patients dead before the 3-year threshold) were also excluded.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eBaseline Evaluation\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003eClinical and neurological evaluation\u003c/h2\u003e \u003cp\u003eAll patients underwent a standardized clinical evaluation including medical history collection, vital parameters, complete physical examination, and PD staging by means of the Hoehn and Yahr (H\u0026amp;Y) scale [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Finally, Charlson comorbidity index was assessed [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eOffice blood pressure measurement\u003c/h2\u003e \u003cp\u003eOffice BP evaluations were carried out between 2 PM and 5 PM, at least 2 h after a meal, in a standardized environment at a room temperature of 71\u0026ndash;75\u0026deg; Fahrenheit. BP values were collected in the supine position (average of the last three BP stable measurements) and every minute during the active standing position with an OMRON automatic sphygmomanometer (HEM-9219T-E, Japan \u0026copy;). Heart rate (HR) values were also collected. OH was defined as a sustained systolic BP drop\u0026thinsp;\u0026ge;\u0026thinsp;20 mm Hg or a diastolic BP drop\u0026thinsp;\u0026ge;\u0026thinsp;10 mm Hg within 3 min of orthostatic test [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. We included in the OH analyses only patients with nOH, defined as having a Δ HR/Δ systolic BP ratio\u0026thinsp;\u0026lt;\u0026thinsp;0.5 beats per minute (bpm)/mmHg [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eAmbulatory Blood Pressure Monitoring\u003c/h2\u003e \u003cp\u003eTwenty-four hours ABPMs were performed with a portable device (Spacelabs 90207, Spacelabs Inc., Redmond, WA, USA \u0026copy;) with appropriate cuff size placed on the non-dominant arm as per the current guidelines [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. BP measurements were taken every 15 min during the daytime and nighttime. Patients were asked to keep a diary of occupational activities, sleep, and awake time, as well as the time of meals.\u003c/p\u003e \u003cp\u003eWe used normal reference thresholds for ABPM and adhered to the definition of weighted BP variability and dipping patterns proposed by the European Society of Hypertension [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. According to a previous study from our group [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] we defined hypotensive episode (Hypo-ep\u003csup\u003e∆15/24h\u003c/sup\u003e) a systolic drop\u0026thinsp;\u0026ge;\u0026thinsp;15 mmHg compared to the average 24-h systolic BP, during the waking period (from awakening to lunch). We considered as significant the presence of at least two hypotensive episodes [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up evaluation\u003c/h2\u003e \u003cp\u003eWe retrospectively reviewed the medical records of each participant. For every outpatient visit we evaluated: the medical history, which included information on treatment, recent falls, fractures, ER accesses and hospitalizations; the neurological evaluation, including the staging of PD motor severity assessed by means of the H\u0026amp;Y scale; and the cognitive status. Dementia was diagnosed when Montreal Cognitive Assessment (MoCA) score was lower than 21/30 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], or when reported at recent comprehensive neuropsychological assessment, or in the presence of incontrovertible symptoms/signs of cognitive impairment associated with functional limitation (e.g., executive or amnestic impairment needing assistance in common activities of daily living) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Mortality data were searched in our electronic archives, which are constantly updated by the regional registry office.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eOutcome Measures and Statistical analysis\u003c/h2\u003e \u003cp\u003eThe potential prognostic role of ABPM hypotensive episodes (Hypo-ep\u003csup\u003e∆15/24h\u003c/sup\u003e) in predicting specific complications, was compared with a well-established predictor, such as office nOH.\u003c/p\u003e \u003cp\u003ePrimary endpoints included mortality for all causes, falls, fractures, and cognitive impairment. Secondary endpoints included hospitalizations, and bed or wheelchair confinement.\u003c/p\u003e \u003cp\u003eCumulative survival for each adverse outcome was evaluated through Kaplan-Meier curves. The sample was divided in patients with and without the following predictors: a) at least two hypotensive episodes (Hypo-ep\u003csup\u003e∆15/24h\u003c/sup\u003e) at the ABPM during the waking period; b) office nOH. Differences between the two groups were assessed by means of the log-rank test. The prognostic role of the same predictors was then evaluated through Cox regression analysis, adjusting for age, Charlson comorbidity index, PD duration and severity (H\u0026amp;Y scale). In both Kaplan-Meier and Cox regression analyses, patients already reporting the adverse outcome at baseline (e.g., patients reporting falls or dementia) were excluded.\u003c/p\u003e \u003cp\u003eContinuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Qualitative variables were expressed as frequencies or percentage values. Normal distribution of continuous variables was tested using the Shapiro-Wilk test. Differences between two independent groups were evaluated using a Student\u0026rsquo;s t-test for continuous variables with normal distribution and the Mann-Whitney test for continuous variables with non-normal distribution. Categorical variables were compared using the chi-square test or Fisher\u0026rsquo;s exact test according to sampling number of analysed groups. Statistical analysis was performed with SPSS (IBM Corp. Released 2017. IBM SPSS, Version 25.0. Armonk, NY: IBM Corp). Statistical significance was considered for p values\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003e The present study was approved by the Institutional Review Committee of Turin (Comitato Etico Interaziendale A.O.U. Citt\u0026agrave; della Salute e della Scienza di Torino \u0026ndash; A.O. Ordine Mauriziano). All subjects submitted their written informed consent.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eInclusion criteria were fulfilled by 143 patients; 44 patients presented exclusion criteria (n\u0026thinsp;=\u0026thinsp;3 had chronic heart failure, n\u0026thinsp;=\u0026thinsp;4 had chronic renal failure, n\u0026thinsp;=\u0026thinsp;12 had diabetes mellitus, n\u0026thinsp;=\u0026thinsp;12 had incomplete clinical data at baseline, n\u0026thinsp;=\u0026thinsp;13 had incomplete clinical data at follow-up, or were lost at follow-up). Therefore, the study population consisted of 99 patients, with a higher prevalence of men (74%), a mean age of 64.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1 (range 34\u0026ndash;79) years, and PD duration of 6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 (range 1\u0026ndash;18) years. The average follow-up duration was 5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7 years (range 1\u0026ndash;10).\u003c/p\u003e \u003cp\u003eAt baseline, 45 patients (45.5%) presented with H\u0026amp;Y stage 1, 38 (38.4%) with stage 2, 15 (15.2%) with stage 3, and one (1.0%) with stage 4, while no patients met the clinical criteria of H\u0026amp;Y stage 5. Previous history of arterial hypertension was present in the 29.3% of patients (n\u0026thinsp;=\u0026thinsp;29). All patients were on dopaminergic treatment, with a levodopa equivalent daily dose (LEDD) of 662.0\u0026thinsp;\u0026plusmn;\u0026thinsp;352.7 mg, while the 31.3% (n\u0026thinsp;=\u0026thinsp;31) of the cohort was on vasoactive drugs (antihypertensive (n\u0026thinsp;=\u0026thinsp;31) and/or antihypotensive (n\u0026thinsp;=\u0026thinsp;24) medications).\u003c/p\u003e \u003cp\u003eOH was detected in 48 patients, but in two cases the Δ HR/ Δ BP ratio indicated the presence of non-neurogenic OH. The remaining 46 nOH patients (46.5%) were included in the analyses.\u003c/p\u003e \u003cp\u003eABPM detected at least two hypotensive episodes (\u0026ge;\u0026thinsp;2 Hypo-ep\u003csup\u003e∆15/24h\u003c/sup\u003e) in 38 patients (38.4%). Clinical and demographical characteristics of patients with and without hypotensive episodes at ABPM are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Sensibility (67.4%), specificity (86.8%), and accuracy (77.8%) of the Hypo-ep\u003csup\u003e∆15/24h\u003c/sup\u003e criterion for the detection of nOH were comparable to those found in our previous study on a different PD population [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], confirming the consistency of the method.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n. 99)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew/ Hypo-ep\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n. 38)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ew/o Hypo-ep\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n.61)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge \u003cem\u003e[years]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex \u003cem\u003e[n.] (%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (26.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.992\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease duration \u003cem\u003e[years]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.163\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up duration \u003cem\u003e[years]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.035\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal LEDD \u003cem\u003e[mg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e662.0\u0026thinsp;\u0026plusmn;\u0026thinsp;352.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e757.1\u0026thinsp;\u0026plusmn;\u0026thinsp;381.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e602.8\u0026thinsp;\u0026plusmn;\u0026thinsp;322.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.034\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVasoactive therapy \u003cem\u003e[n.] (%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (44.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (22.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious arterial hypertension \u003cem\u003e[n.] (%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (29.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (42.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (21.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.027\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enOH \u003cem\u003e[n.] (%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (46.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (81.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAmbulatory blood pressure monitoring\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h SBP \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e121.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e118.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.191\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h MBP \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.170\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h DBP \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.541\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaytime SBP \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e121.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e121.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e121.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.949\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaytime MBP \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.968\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaytime DBP \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.664\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaytime HR \u003cem\u003e[bpm]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.982\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNighttime SBP \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115.2\u0026thinsp;\u0026plusmn;\u0026thinsp;14.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e122.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e110.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNighttime MBP \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNighttime DBP \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNighttime HR \u003cem\u003e[bpm]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.087\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaytime SBP load \u003cem\u003e[%]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.7\u0026thinsp;\u0026plusmn;\u0026thinsp;20.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.4\u0026thinsp;\u0026plusmn;\u0026thinsp;18.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.7\u0026thinsp;\u0026plusmn;\u0026thinsp;22.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.528\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaytime DBP load \u003cem\u003e[%]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.0\u0026thinsp;\u0026plusmn;\u0026thinsp;19.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.1\u0026thinsp;\u0026plusmn;\u0026thinsp;17.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.4\u0026thinsp;\u0026plusmn;\u0026thinsp;19.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.653\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNighttime SBP load \u003cem\u003e[%]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.7\u0026thinsp;\u0026plusmn;\u0026thinsp;33.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.2\u0026thinsp;\u0026plusmn;\u0026thinsp;36.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.0\u0026thinsp;\u0026plusmn;\u0026thinsp;27.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNighttime DBP load \u003cem\u003e[%]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.0\u0026thinsp;\u0026plusmn;\u0026thinsp;31.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.6\u0026thinsp;\u0026plusmn;\u0026thinsp;35.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.5\u0026thinsp;\u0026plusmn;\u0026thinsp;25.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReverse dipping \u003cem\u003e[n.] (%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (30.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ew-BPV \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypo-ep\u003csup\u003eΔ15/24 h\u003c/sup\u003e \u003cem\u003e[n.]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOffice blood pressure values\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP (supine) \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130.6\u0026thinsp;\u0026plusmn;\u0026thinsp;16.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e140.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e124.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP (supine) \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR (supine) \u003cem\u003e[bpm]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.151\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP (orthostatism 1\u0026rsquo;) \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e116.0\u0026thinsp;\u0026plusmn;\u0026thinsp;21.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118.2\u0026thinsp;\u0026plusmn;\u0026thinsp;25.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e114.6\u0026thinsp;\u0026plusmn;\u0026thinsp;17.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.405\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP (orthostatism 1\u0026rsquo;) \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.2\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.389\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP (orthostatism 3\u0026rsquo;) \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115.5\u0026thinsp;\u0026plusmn;\u0026thinsp;18.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116.8\u0026thinsp;\u0026plusmn;\u0026thinsp;21.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e114.8\u0026thinsp;\u0026plusmn;\u0026thinsp;16.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.600\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP (orthostatism 3\u0026rsquo;) \u003cem\u003e[mmHg]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.825\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR (orthostatism) \u003cem\u003e[bpm]\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85.2\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.817\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eLEDD: levodopa equivalent daily dose; nOH: neurogenic orthostatic hypotension; SBP: systolic blood pressure; MBP; mean blood pressure; DBP: diastolic blood pressure; BPV: blood pressure variability; Hypo-ep\u003csup\u003eΔ15/24 h\u003c/sup\u003e: hypotensive episode at Ambulatory Blood pressure Monitoring; HR: heart rate; w-BPV: weighted blood pressure variability; w/: with; w/o: without\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePatients with hypotensive episodes were older and treated with higher doses of dopaminergic therapy; they had 3-fold higher prevalence of nOH (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 2-fold higher prevalence of arterial hypertension (p\u0026thinsp;=\u0026thinsp;0.027). Moreover, they showed higher nocturnal BP values (p\u0026thinsp;=\u0026thinsp;0.001), BP loads (p\u0026thinsp;=\u0026thinsp;0.001) and BP variability (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), together with a 3-fold higher prevalence of reverse dipping pattern (p\u0026thinsp;=\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAt baseline, the prevalence of falls in the entire sample was 14.1% (n\u0026thinsp;=\u0026thinsp;14), significantly higher in patients with hypotensive episodes at ABPM (26.3% vs. 6.6%, p\u0026thinsp;=\u0026thinsp;0.008). Dementia was reported in 10.1% of patients (n\u0026thinsp;=\u0026thinsp;10), with a 2-fold higher prevalence (15.8% vs. 6.6%) among patients with hypotensive episodes at ABPM, not reaching the statistical threshold (p\u0026thinsp;=\u0026thinsp;0.128). No patient was bedridden/wheelchair-bound or reported recent fractures or hospitalization.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eOutcome evaluation\u003c/h2\u003e \u003cp\u003eDuring the follow-up, we observed a high incidence of falls (40.0%; 34/85, excluding patients already reporting falls at baseline), dementia (37.1%; 33/89, excluding patients already demented at baseline), fractures (22.2%; 22/99), hospitalization (32.3%; 32/99), and bed or wheelchair confinement (13.1%; 13/99). Mortality rate was 13.1% (13/99), with a mean survival time from baseline of 5.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7 years and a mean disease duration at death of 15.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1 years. Both incidence and prevalence of falls were significantly higher in patients with ABPM hypotensive episodes (Incidence: 57.1% vs. 31.6%, p\u0026thinsp;=\u0026thinsp;0.022; Prevalence: 68.4% vs. 36.1%, p\u0026thinsp;=\u0026thinsp;0.002). The same observations were found for dementia (Incidence: 53.1% vs. 28.1%, p\u0026thinsp;=\u0026thinsp;0.017; Prevalence: 60.5% vs. 32.8%, p\u0026thinsp;=\u0026thinsp;0.006). Patients with ABPM hypotensive episodes presented with significant higher incidence of fractures (34.2% vs. 14.8%, p\u0026thinsp;=\u0026thinsp;0.023), while for hospitalization and bed/wheelchair confinement the difference did not reach full statistical significance (42.1% vs. 26.2%, p\u0026thinsp;=\u0026thinsp;0.078; and 21.1% vs. 8.2%, p\u0026thinsp;=\u0026thinsp;0.064; respectively). Mortality was higher in patients with ABPM hypotensive episodes, with a trend towards statistical significance (21.1% vs. 8.2%, p\u0026thinsp;=\u0026thinsp;0.064).\u003c/p\u003e \u003cp\u003eThe Kaplan-Meier analysis revealed that the presence of hypotensive episodes at ABPM was associated with earlier onset of falls (4.9 years (95% CI 3.8-6.0) vs. 7.9 years (7.1\u0026ndash;8.7); p\u0026thinsp;=\u0026thinsp;0.001), fractures (6.4 years (95% CI 5.3\u0026ndash;7.6) vs. 9.0 years (8.4\u0026ndash;9.6); p\u0026thinsp;=\u0026thinsp;0.004), hospitalizations (5.3 years (95% CI 4.1\u0026ndash;6.4) vs. 8.2 years (95% CI 7.4-9.0); p\u0026thinsp;=\u0026thinsp;0.009), bedridden/wheelchair confinement (7.1 years (95% CI 6.6\u0026ndash;7.7) vs. 9.4 years (95% CI 8.8\u0026ndash;9.9); p\u0026thinsp;=\u0026thinsp;0.032), and dementia (5.0 years (95% CI 4.0\u0026ndash;6.0) vs. 8.1 years (7.2\u0026ndash;8.9); p\u0026thinsp;=\u0026thinsp;0.001). Patients with hypotensive episodes at ABPM also showed a shorter survival (8.0 years (95% CI 7.3\u0026ndash;8.7) vs. 9.5 years (95% CI 9.0\u0026ndash;10.0); p\u0026thinsp;=\u0026thinsp;0.009) (Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eOffice OH was related to earlier onset of falls (5.8 years (95% CI 4.7-7.0) vs. 7.7 years (6.9\u0026ndash;8.6); p\u0026thinsp;=\u0026thinsp;0.045), earlier development of cognitive impairment (6.0 years (95% CI 5.0\u0026ndash;7.0) vs. 7.8 years (95% CI 6.9\u0026ndash;8.7); p\u0026thinsp;=\u0026thinsp;0.034), and death (8.0 years (95% CI 7.3\u0026ndash;8.7) vs. 9.5 years (9.1\u0026ndash;10.0); p\u0026thinsp;=\u0026thinsp;0.048), while a trend towards statistical significance was observed for hospitalizations (p\u0026thinsp;=\u0026thinsp;0.086), fractures (p\u0026thinsp;=\u0026thinsp;0.089), and bedridden/wheelchair confinement (p\u0026thinsp;=\u0026thinsp;0.057) (Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eAfter correction for potential confounders, such as age, Charlson comorbidity index, PD duration, and PD severity at baseline, the Cox-Regression analysis showed a significant association between the presence of hypotensive episodes at ABPM and falls (OR 3.626, 95% CI 1.7\u0026ndash;7.6; p\u0026thinsp;=\u0026thinsp;0.001), hospitalizations (OR 2.016, 95% CI 1.2\u0026ndash;4.5; p\u0026thinsp;=\u0026thinsp;0.038), and dementia (OR 2.926, 95% CI 1.3\u0026ndash;6.5; p\u0026thinsp;=\u0026thinsp;0.008); the association with fractures (OR 2.155, 95% CI 0.9\u0026ndash;5.4; p\u0026thinsp;=\u0026thinsp;0.092) showed a trend towards statistical significance, while no association was found with bed/wheelchair confinement (OR 2.462, 95% CI 0.7\u0026ndash;8.5; p\u0026thinsp;=\u0026thinsp;0.155) or mortality (OR 1.352, 95% CI 0.4\u0026ndash;5.1; p\u0026thinsp;=\u0026thinsp;0.655).\u003c/p\u003e \u003cp\u003eAfter the same corrections, office nOH showed inferior prognostic value for the adverse outcomes considered, only presenting a significant association with falls (OR 2.022, 95% CI 1.2\u0026ndash;4.1; p\u0026thinsp;=\u0026thinsp;0.039) and dementia (OR 1.908, 95% CI 1.1-4.0; p\u0026thinsp;=\u0026thinsp;0.048). Details are presented in Fig.\u0026nbsp;3.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOH is a frequent and detrimental feature of PD; however, in clinical practice its diagnosis is still overlooked. One of the main features limiting a correct OH detection in an outpatient setting is the presence of BP circadian fluctuations. In this context, we explored the prognostic role of hypotensive episodes detected at the ABPM in predicting mortality and specific adverse outcomes in a large cohort of parkinsonian patients.\u003c/p\u003e \u003cp\u003eWe retrospectively evaluated mortality and the occurrence of important milestones of disability during an up-to-10-year follow-up and compared them between patients with and without ABPM hypotensive episodes. Finally, we evaluated the same differences between patients with and without office nOH.\u003c/p\u003e \u003cp\u003eWe found a significant association between ABPM hypotensive episodes and earlier onset of falls, cognitive impairment, hospitalizations, fractures, being bedridden or wheelchair-bound, and mortality. After correcting for potential confounders, hypotensive episodes retained a significant correlation with higher risk of falls, hospitalizations, and cognitive impairment. On the other hand, office nOH was associated with earlier onset of falls, cognitive impairment, and death, but only falls and cognitive impairment maintained the association after the adjusted analysis.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003eAssociation with falls\u003c/span\u003e. nOH is a well-known risk factor for falls in general population, and it is considered one of the main issues to be targeted to reduce the risk of falls, together with functional status, home safety, and vision disturbances [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In PD patients, OH is independently associated with an up-to-10-fold higher risk ok falls [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, daily BP profile is characterized by significant circadian fluctuations, and is influenced by many intrinsic and extrinsic features, such as sleep, temperature, meals, fluid intake, exercise, evaluation setting (e.g., in-hospital vs. home), and drugs intake. Therefore, the simple in-office evaluation of OH could be burdened by a certain amount of inaccuracy, while the evaluation by means of ABPM could led to a more detailed identification of hypotensive episodes, besides providing important information on supine hypertension, a frequently overlooked feature of cardiovascular dysautonomia [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Our results seem to confirm this assumption, since both ABPM episodes and office OH were associated with higher risk of falls, but the former showed a stronger and more significant correlation.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003eAssociation with cognitive impairment.\u003c/span\u003e The association of OH and cognitive impairment has been detected both in general population and in patients with Alzheimer\u0026rsquo;s Disease or vascular dementia [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e][\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e][\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Large population studies highlighted an increased risk of developing dementia in patients with OH, ranging from 1.2-to-2-fold [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. This association results even stronger in α-synucleinopathies, with a 3-to-8-fold higher risk of cognitive impairment in PD patients with OH [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e][\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e][\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePossible pathophysiological mechanisms are multiple and still to be fully clarified [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. While some authors postulate a phenotypical association between dysautonomia, cognitive impairment, and worse motor impairment [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], other works reported that repeated bouts of cerebral hypoperfusion, along with altered regional patterns in supine cerebral blood flow and the presence of supine hypertension, could lead to greater burden of white matter lesions and cerebral atrophy, thus favoring the development of cognitive impairment [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e][\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e][\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e][\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. However, these two hypotheses are not mutually exclusive, and both diffuse pathology and cerebral hypoperfusion may play a synergistic role [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]: the possibility exists that, in the context of a diffuse neurodegeneration, chronic OH and impaired dynamic cerebral auto-regulation [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] contribute to the worsening of neuropathology, probably by means of hypoxia-induced neurodegeneration, rather than by favoring α-synuclein deposition or vascular pathology [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. In our study, we observed a significant association between ABPM hypotensive episodes (and in-office OH) and dementia, even after adjusting our analyses for many confounding variables that may explain the phenotypical association between OH and dementia (i.e., age, Charlson comorbidity index, PD duration and motor severity), thus suggesting a prevalent causative or synergistic role of OH in determining cognitive impairment. This observation seems in line with the recent findings by Ruiz Barrio and colleagues [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], who in a large pathological study on PD and Multiple System Atrophy patients observed an independent association between OH and cognitive impairment, but did not find differences in α-synuclein, β-amyloid, or tau pathology in patients with and without OH. Finally, in the present study, the strength and the significance of the association with cognitive impairment was greater for ABPM hypotensive episodes than office OH, further confirming the usefulness of ABPM in capturing the complexity of the circadian fluctuation of BP, and suggesting a possible role of BP variability in determining worse functional outcomes [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003eAssociation with hospitalization.\u003c/span\u003e About 80,000 hospitalizations in the United States each year are related to OH, mainly in the elderly population [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e][\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. In PD patients, OH is an independent determinant of greater health care utilization [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], both for the potential consequences of the hypotensive episodes (falls, syncopes, head injury, fractures) and for the presence of other clinical features potentially responsible for hospitalization, which usually coexist with OH, such as ageing, diabetes, and cardiovascular comorbidities [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. In our sample, ABPM hypotensive episodes were significantly associated with a 3-year earlier need for hospitalization and a 2-fold higher risk of hospitalization, compared to patients without episodes. Surprisingly, office OH did not show significant correlation at the adjusted Cox regression analysis, possibly due to the long-term follow-up in a relatively aged population, which resulted in a high probability of observing hospitalization for causes other than OH.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003eAssociation with fractures and bed/wheelchair confinement.\u003c/span\u003e Although univariate Kaplan-Meier analysis showed earlier occurrence of fractures and bed or wheelchair confinement in patients with hypotensive episodes or office OH, similarly to previous reports [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e][\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e], these observations were not confirmed at the corrected analysis, probably due to the inclusion, among the considered confounders, of age, disease duration, and motor disability, which are well-known features associated with these detrimental disability milestones in PD and other α-synucleinopathies [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e][\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e][\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003eAssociation with mortality.\u003c/span\u003e Autonomic dysfunction [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] and, specifically, OH [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e] have been associated with shorter survival in PD. In our sample, mortality was significantly associated with ABPM episodes and OH, with a 1.5-year shorter survival. However, the corrected analyses did not confirm this association, probably due to the relatively low rate of death during the follow-up.\u003c/p\u003e \u003cp\u003eThe main strengths of our study include the long-term follow-up, with seriate and standardized clinical evaluations, as well as rigorous patients\u0026rsquo; selection. However, some limitations should be taken into account. First, the relatively low sample size. Second, the retrospective design may have hampered the collection of important clinical data, including the disability milestones considered in the study, although we included only patients with a periodic and standardized follow-up in order to minimize this possible bias. Third, the absence of seriate collection of office OH or ABPM data, may have underestimated the incidence of new OH; however, if this were the case, we would have probably observed an even greater association between hypotensive episodes and disability milestones or mortality. Fourth, the definition of nOH was not based on cardiovascular autonomic test assessment, although the application of the recently proposed Δ HR/Δ systolic BP index [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] should have attenuated this bias. Fifth, the lack of a comprehensive evaluation of the autonomic symptoms other than OH limits firm considerations on a causal relationship between hypotensive episodes/OH and the development of disability milestones.\u003c/p\u003e \u003cp\u003eIn conclusion, our findings highlight the potential role of repeated hypotensive episodes in determining worse outcomes in PD patients, confirming and strengthening, by means of a 10-year follow-up, previous Literature data. Though, our study introduces a novel element that has so far received little consideration. In fact, we demonstrated the usefulness of ABPM in predicting detrimental PD complications, with apparent greater accuracy compared to simple OH bedside evaluation, due to its higher capability in capturing the complexity of BP circadian fluctuations. Thus, a wider application of ABPM, both in clinical practice and in research context, is warranted to enhance the comprehension of the relationship between cardiovascular dysautonomia and PD progression trajectories.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFVa, MV, MMT, AC, VM, CD, GS, MG, FVe, LL, SM: None\u003c/p\u003e\n\u003cp\u003eAR:\u0026nbsp;he received grant support and speaker honoraria from Abbvie, speaker honoraria from Chiesi Farmaceutici and travel grants from Lusofarmaco, ChiesiFarmaceutici, Medtronic, and UCB Pharma.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAM: he received supported from the NIH (KL2 TR001426), speaker honoraria from CSL Behring, Abbvie, Abbott, Theravance and Cynapsus Therapeutics. He has received grant support from Lundbeck and Abbvie\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: none\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMerola A, Sawyer RP, Artusi CA et al (2018) Orthostatic hypotension in Parkinson disease: Impact on health care utilization. Parkinsonism Relat Disord 47:45\u0026ndash;49. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.parkreldis.2017.11.344\u003c/span\u003e\u003cspan address=\"10.1016/j.parkreldis.2017.11.344\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVelseboer DC, de Haan RJ, Wieling W et al (2011) Prevalence of orthostatic hypotension in Parkinson\u0026rsquo;s disease: a systematic review and meta-analysis. 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Neurology 85:1554\u0026ndash;1561. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1212/WNL.0000000000002086\u003c/span\u003e\u003cspan address=\"10.1212/WNL.0000000000002086\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"clinical-autonomic-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"autr","sideBox":"Learn more about [Clinical Autonomic Research](http://link.springer.com/journal/10286)","snPcode":"10286","submissionUrl":"https://www.editorialmanager.com/autr/default2.aspx","title":"Clinical Autonomic Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Parkinson’s disease, orthostatic hypotension, disability milestones, adverse outcomes, ambulatory blood pressure monitoring, hypotensive episodes","lastPublishedDoi":"10.21203/rs.3.rs-3904996/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3904996/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003ePurpose.\u003c/b\u003e Neurogenic orthostatic hypotension (nOH) is a frequent non-motor feature of Parkinson\u0026rsquo;s disease (PD), associated with adverse outcomes. Recently, 24-hour ambulatory BP monitoring (ABPM) has been shown to diagnose nOH with good accuracy (in the presence of at least 2 episodes of systolic BP drop\u0026thinsp;\u0026ge;\u0026thinsp;15 mmHg compared to the average 24-h). This study aims at evaluating the prognostic role of ABPM-hypotensive episodes in predicting PD disability milestones and mortality and comparing it to well-defined prognostic role of nOH.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods.\u003c/b\u003e PD patients who underwent ABPM from January 2012 to December 2014 were retrospectively enrolled and assessed for the development of falls, fractures, dementia, bed/wheelchair confinement, hospitalization, mortality, during an up-to-10-year follow-up.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults.\u003c/b\u003e Ninety-nine patients (male 74%; age: 64.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1 years; PD duration: 6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 years) were enrolled. At baseline, 38.4% of patients had ABPM-hypotensive episodes and 46.5% had bedside nOH.\u003c/p\u003e \u003cp\u003eAt Kaplan-Meier analysis patients with ABPM-hypotensive episodes had an earlier onset of falls (p\u0026thinsp;=\u0026thinsp;0.001), fractures (p\u0026thinsp;=\u0026thinsp;0.004), hospitalizations (p\u0026thinsp;=\u0026thinsp;0.009), bed/wheelchair confinement (p\u0026thinsp;=\u0026thinsp;0.032), dementia (p\u0026thinsp;=\u0026thinsp;0.001), and showed a shorter survival (8.0vs9.5 years; p\u0026thinsp;=\u0026thinsp;0.009). At Cox regression analysis (adjusted for age, disease duration, Charlson Comorbidity Index, and H\u0026amp;Y stage at baseline) a significant association was confirmed between ABPM-hypotensive episodes and falls (OR:3.626; p\u0026thinsp;=\u0026thinsp;0.001), hospitalizations (OR:2.016; p\u0026thinsp;=\u0026thinsp;0.038), and dementia (OR:2.926; p\u0026thinsp;=\u0026thinsp;0.008), while bedside nOH was only associated with falls (OR 2.022; p\u0026thinsp;=\u0026thinsp;0.039) and dementia (OR:1.908; p\u0026thinsp;=\u0026thinsp;0.048).\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusion.\u003c/b\u003e The presence of at least two ABPM-hypotensive episodes independently predicted the development of falls, dementia, and hospitalization, showing a stronger prognostic value than the simple bedside assessment.\u003c/p\u003e","manuscriptTitle":"Hypotensive episodes at 24-h Ambulatory Blood Pressure Monitoring predict adverse outcomes in Parkinson’s Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-06 17:04:58","doi":"10.21203/rs.3.rs-3904996/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-01-31T19:24:54+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-01-31T17:46:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-30T15:44:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Clinical Autonomic Research","date":"2024-01-27T10:29:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"clinical-autonomic-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"autr","sideBox":"Learn more about [Clinical Autonomic Research](http://link.springer.com/journal/10286)","snPcode":"10286","submissionUrl":"https://www.editorialmanager.com/autr/default2.aspx","title":"Clinical Autonomic Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8d8d1c1f-fc84-4f3c-9ab5-9f34680fae70","owner":[],"postedDate":"February 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-02T00:54:04+00:00","versionOfRecord":{"articleIdentity":"rs-3904996","link":"https://doi.org/10.1007/s10286-024-01030-7","journal":{"identity":"clinical-autonomic-research","isVorOnly":false,"title":"Clinical Autonomic Research"},"publishedOn":"2024-04-25 00:54:04","publishedOnDateReadable":"April 25th, 2024"},"versionCreatedAt":"2024-02-06 17:04:58","video":"","vorDoi":"10.1007/s10286-024-01030-7","vorDoiUrl":"https://doi.org/10.1007/s10286-024-01030-7","workflowStages":[]},"version":"v1","identity":"rs-3904996","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3904996","identity":"rs-3904996","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}